The gastrointestinal tract is a highly complex organ in which multiple dynamic physiological processes are tightly coordinated while interacting with a dense and extremely diverse microbial population. From establishment in early life, through to host-microbe symbiosis in adulthood, the gut microbiota plays a vital role in our development and health. The effect of the microbiota on gut development and physiology is highlighted by anatomical and functional changes in germ-free mice, affecting the gut epithelium, immune system, and enteric nervous system. Microbial colonisation promotes competent innate and acquired mucosal immune systems, epithelial renewal, barrier integrity, and mucosal vascularisation and innervation. Interacting or shared signalling pathways across different physiological systems of the gut could explain how all these changes are coordinated during postnatal colonisation, or after the introduction of microbiota into germ-free models. The application of cell-based in vitro experimental systems and mathematical modelling can shed light on the molecular and signalling pathways which regulate the development and maintenance of homeostasis in the gut and beyond. This article is protected by copyright. All rights reserved.